1. Field of the Invention
The present invention relates to a composition for storing tissues prior to transplantation, and a method for storing such tissues. In one embodiment of the invention, the tissues are human tissues.
2. Background Information
In perfused rat livers stored in cold Euro-Collins solution for 24 hours, hepatic parenchymal cells exclude trypan blue; however, nonparenchymal cells lose viability as quickly as 8 hours upon reperfusion (Caldwell-Kenkel et al, Transplantation 1988; 5:834). These data have suggested to the present inventors that viability of parenchymal cells in liver grafts prior to transplantation (e.g., assessed from ATP levels measured chemically or by .sup.31 P NMR (Kamike et al, Transplantation 1988; 45:138) is a poor predictor of surgical outcome. Further, it follows from this reasoning that preservation of nonparenchymal cells is critical for successful liver transplantation.
In perfused livers, the injury to non-parenchymal cells following cold storage involves mainly sinusoidal endothelium (Caldwell-Kenkel et al, Hepatology 1989; 10:292). Further, in an in vivo model of liver transplantation, disturbances in the microcirculation and an injury to about 20% of hepatic parenchymal cells has been observed 24 hours postoperatively. However, it was found that the injury to the hepatic parenchymal cells could be prevented almost entirely by rinsing the organ with nitrogen-saturated buffer. Based on the results of these two models, it was concluded that a reperfusion injury occurs in liver transplantation (Thurman et al, Transplantation 1988; 46:502).
Following cold storage and reperfusion, activation of Kupffer cells was detected based on electron microscopy (Caldwell-Kenkel et al, Hepatology 1988; 8:289), and uptake of colloidal carbon (Thurman et al, The Kupffer Cell Fndn., Rijswijk, The Netherlands, 1989: 159). Further, an inhibitor of Kupffer cell function, methyl palmitate, diminished particle phagocytosis and increased postoperative survival time nearly 3-fold. Kupffer cells produce a number of highly toxic peptides including tumor necrosis factor and platelet activating factor and they release a variety of potent proteases on activation. Calcium is most likely involved in these processes, since prostanoid production by Kupffer cells was increased by the calcium ionophore, A23187 (Dieter et al, Eur. J.Biochem 1988; 255:61).
This suggested to the inventors that a calcium channel blocker would have a good effect on tissues being stored prior to transplantation.